Methamphetamine (meth) use is the number one drug problem in the western United States, and a dramatic increase in its use has been reported nationally. Meth use has been linked to high-risk sexual behavior and associated increases in HIV/STI prevalence, but the majority of work has focused on men who have sex with men. Under previous funding we demonstrated the efficacy of a social cognitive theory (SCT)-based intervention designed for HIV-negative heterosexual meth users. We also demonstrated high levels of depressive symptoms in this group, and that individuals with high levels of depression and meth use benefited less from our intervention program. To fully address the role of depressive symptoms and meth use in relation to sexual behavior change, we will, in this renewal, extend our primary treatment goal of reducing sexual risk behavior to include two secondary treatment goals: 1) reduce depressive symptoms;and 2) reduce/abate the use of meth. By simultaneously addressing all three problem areas we expect to observe significant reductions in high-risk sexual behavior in this population. In the proposed five-year study, 400 heterosexually identified men and women who are active meth users and report having unprotected sex will be randomly assigned to one of two conditions: 1) a nine-session Cognitive Behavior Therapy (CBT/SCT)-based safer sex counseling program focused on mood regulation, meth reduction/cessation, and safer sex practices;or a standard care comparison condition (time equivalent with the CBT program). Followup assessments for all subjects will be conducted at 4, 8, and 12 months after the baseline assessment. A variety of outcomes will be examined (e.g., reductions in unprotected vaginal sex, number of STIs, reductions in depressive symptoms and meth use). Subgroup differences in the efficacy of the intervention based on individual factors (e.g., ethnicity, gender) and psychosocial factors (e.g., experiences of abuse) will also be examined. To date, very few intervention studies have focused on the high risk sexual behaviors of heterosexual meth users. Accordingly, the results of this study will have important implications for reducing the risks of HIV and STIs and other negative health effects of ongoing meth use among the growing number of heterosexual meth users in the United States.